Displacement-activated medical check valve

ABSTRACT

A displacement-activated medical check valve is provided for selectively opening and closing medicinal fluid communication. The check valve includes a flexible elastomeric member that has a proximal end and a distal end and has a sealed perforation defined at least partially through the flexible elastomeric member. A housing receives the flexible elastomeric member so that it can be displaced along the length thereof. A contact member is provided for engaging the distal end of the elastomeric member when at least a portion of the elastomeric member is displaced against the contact member. The elastomeric member and the sealed perforation are sized and configured such that the perforation is shortened and thereby compressed open when the elastomeric member is compressed against the contact member. When a compressive force is removed the elastomeric member rebounds to close the perforation.

This is a continuation of application Ser. No. 08/231,430 filed Apr. 22,1994, now U.S. Pat. No. 5,522,804, which is a Continuation in Part ofapplication Ser. No. 08/248,646 filed May 25, 1994, now U.S. Pat. No.5,549,651 which is a continuation-in-part of my U.S. patent applicationentitled, Sequential Aspiration and Injection Syringe, filed on Feb. 15,1994 (Application Ser. No. 08/196,455 now abandoned and havingco-inventor Mark Larkin and assigned to the present inventor) (thedisclosure of which is hereby incorporated by reference as if completelydisclosed herein). The aforementioned application presents thebackground of multi-chambered syringes which are used for sequentialinjection and/or the mixing of drugs and solutions. Additionalbackground of enclosed drug-mixing systems is provided in U.S. Pat. No.4,614,267. As described within the backgrounds of the many patentspresented in the aforementioned application, it is advantageous to storea drug in a powdered or liquid form and then mix the drug in the sameenclosure which is subsequently placed in fluid connection with thepatient. More specifically, it is advantageous to provide mixing withina syringe so that reconstitution within a separate drug vial becomesunnecessary. This, however, must be provided at minimum cost and wouldpreferably utilize materials to store the drug, such as glass, whichhave been determined appropriate by the U.S. Food and DrugAdministration for long-term storage of drugs so that the evaluation ofthe leaching or interaction between the drug and the drug container isunnecessary. Such compatibility evaluations are associated withconsiderable delay and development expenses. PCT Patent Application #WO92/01485 describes a syringe for this purpose having a glass insert andincluding dual pistons. The syringe, however, includes a complex barrelhaving multiple bores and bypass regions. This syringe requires complexmolding, assembly, and sealing. However, with respect to drugadministration systems, reduced cost, simplicity of design and molding,versatility of use, compatibility with automated drug dispensingsystems, and ease of sterile assembly and use are the major factorsdefining success. It is particularly useful to provide a system using aconventional type glass vial and a convention smooth bore syringe barrelof the type in wide use and inexpensively molded of polypropylene inmass quantities and in a wide variation of bore sizes. As will beevident from the following discussion, the present invention operates toovercome many existing problems in the present art.

BACKGROUND AND SUMMARY OF THE INVENTION

The sequential aspiration, mixing, and injection syringe includes abarrel having an inner wall and a main bore which is preferablyconventional and smooth along substantially its entire length. Thesyringe includes a piston assembly having a proximal portion and adistal portion and a connecting element intermediate the portions. Theportions are sized to be received into a main bore of the barrel and tofit snugly against the barrel wall. This distal portion preferablyincludes at least one projecting lateral member for engaging the innerwalls of the barrel, thereby effectively fixing the position of thedistal portion at a maximally advanced position along the barrel whichpreferably adjacent the distal end of the barrel, although the positioncould be midway along the barrel. After the pistons have been receivedinto the barrel, the proximal portion is moveable along the barrel awayfrom the distal portion and moveable along the barrel toward the distalportion to define a variable volume mixing chamber intermediate theproximal portion and the distal portion. The connecting element can be afluid reservoir or a drug vial which can be comprised of glass or theconnecting element can be a conduit or tube, or can be a tether or othertensile element. The glass vial can have a proximal end and a distalend. In one embodiment, both ends of the vial are open. The proximalportion can be a piston and can be positioned to occlude the proximalend and the distal portion can be a stopper to occlude the distal end ofa drug vial or the distal end of a fluid reservoir or tube. Theconnecting element provides for mutually equivalent advancement of theproximal and distal portions along the barrel. The combined pistonassembly and the connecting element can be seen to represent a reservoiror drug vial piston connectable to a syringe handle. The distal stopperis displaceable from the fluid reservoir or drug vial by retraction ofthe reservoir or vial away from the distal stopper and by frictional orother engagement of the distal stopper and the barrel after thereservoir or vial and the attached piston assembly have been moved to anadvanced position and then the reservoir or vial is retracted from theadvanced position. This allows for retraction of the proximal pistonaway from the distal stopper after displacement of the stopper fromsealing engagement with the fluid reservoir or drug. In severalembodiments, the proximal piston is further moveable along the vialtoward the distal stopper. Relative advancement of the proximal pistonalong the vial can be caused by advancement of the handle in oneembodiment wherein the proximal piston is attached to the handle. Inanother embodiment, wherein the proximal piston is connected to thedisplaced distal stopper by a tensile element, relative advancement isachieved by retraction of the vial and subsequent tensile forcetransmitted through the tensile element. The distal portion and theproximal portion are preferably carried by the drug vial, the distalportion being displaceable from the drug vial to open the vial into themixing chamber, the proximal portion being moveable along the vial todisplace the drug from the vial into the mixing chamber, the proximalportion effectively converting the open-ended drug vial into aclosed-ended vial piston and thereafter functioning to push the drugsolution within the mixing chamber out of the syringe and into arecipient with minimal deadspace-trapped drug remaining within thesyringe after injection.

A method of drug injection is provided using an embodiment having a mainpiston or vial piston having a handle. The vial piston includes a drugvial having a proximal end and a distal end and containing stopperpiston assembly having a proximal portion connected to a distal portionby a connecting element which can be a tensile element or which can bethe drug vial itself, as will be described. The syringe operates, afterassembly, to achieve the following drug injection method with a singleretraction and advancement of the handle, steps of: 1. aspirate diluentinto the main bore; 2. open the end of a drug vial into the main bore;3. positively expel the drug from the vial; 4. subsequently convert anopen-ended drug vial into a closed-ended injection piston; 5. inject themixed drug and diluent with minimal residual drug remaining in thesyringe after injection.

As noted, the present invention can utilize a drug container or vialwhich can be cylindrical for insertion into a syringe barrel. The drugvial is preferably made of glass or other material which can safelycontain a large variety of different drugs, either in powder or liquidform. In one embodiment, the drug vial includes a closed bottom orproximal end which may include a small air vent and an open top ordistal end which is preferably widely open and can, therefore, easily befilled by conventional automated drug dispensing systems. The drug vialcan include a narrow neck and larger body to facilitate handling byautomated equipment. The drug vial further preferably includes an outerhousing member which can be polymeric. At least one sliding member ispreferably provided about the vial to slidably engage the syringe barrelbore to facilitate advancement and retraction of the drug vial along thesyringe barrel bore. The sliding member can be a thin robber boot orsleeve. Alternatively, the polymeric housing member may itself be sizedto sealingly engage the bore. The sliding member can be a rubber wiperof the type utilized in conventional syringe pistons or can be an o-ringor soft polymeric ring or otherwise fashioned. The sliding member ispreferably carried by the homing or vial and may be positioned proximal,distal to, or along the length of the housing or vial. The outer memberfurther can have a recess for receiving the retainer of the handle of aconventional syringe piston or, alternatively, the handle can be moldedintegrally with the outer vial housing member. The vial can, therefore,be connected to or contained within the handle or can be integral with ahandle. In an embodiment, the vial and handle are made of glass and areintegral and molded together, thereby eliminating the need for the outerpolymeric housing member. In one embodiment, the vial piston includes apiston stopper assembly with a proximal stopper portion for positioningadjacent the closed end of the drug vial and a distal stopper pistonportion for occluding the open end of the drug vial. Both portions canbe comprised of conventional material utilized for rubber stoppers indrug vials so that contact with the drug and the rubber stopper pistonassembly is provided, as is conventional, thereby eliminating thepotential for material-related incompatibility. The proximal and distalportions are connected or linked by the drug vial and can be carried bythe drug vial. In one embodiment, the portions are further preferablyconnected by a tether or by bands or other tensile connecting elementswhich can be comprised of conventional material used in the constructionof rubber stopper pistons so as again to allow direct contact with thedrug within the glass container without the need for further study todetermine compatibility. The two stopper pistons can be molded as asingle part with the connecting rubber tether. In one embodiment, a ventis provided for providing vent connection between the proximal face orend of the proximal piston and the atmosphere or between the proximalface of the proximal piston and the distal face or end of the distalstopper. In one preferred embodiment, the vent passes through thetether, the tether comprising a hollow tube having a bore and extendingto connect bores through the proximal piston and the distal stopper.This defines a flexible tether vent which operates to limit retractionmovement of the proximal piston, thereby to cause advancement of theproximal piston relative to the retracting drug vial and further to ventfluid or air into the drug vial intermediate the proximal piston and theclosed end to permit advancement and to allow enlargement of anotherwise sealed nascent proximal compartment within the vial and tofill the enlarging proximal compartment with fluid. In anotherembodiment, the vent passes through a small opening in the otherwiseclosed bottom of the drug vial, the vent being occluded by the proximalpiston prior to use. The vent can pass into a large volume space withina hollow handle to provide a sealed source of sterile vented atmosphereor liquid with a minimal induction of negative pressure. The width ofthe outer wiper may be varied so as to allow use of the same housing andvial within syringes of variable diameter and volume. This allowsmodification of only the wiper when different volumes of diluent areintended for use with, for example, a powdered drug so that a widevariety of variable sized vials and housings need not be constructed forsyringes having bores of variable diameters.

In the manufacture of one preferred embodiment having a drug vial with aclosed bottom, the proximal piston is inserted into the glass vial andthis can be performed, for example, by radial compression of theproximal piston and insertion such that the proximal piston is fullyadvanced against the closed bottom of the glass vial. The tether orbands are preferably of adequate length to extend out through the opentop of the glass vial such that the top or distal stopper does not, atthis time, occlude the opening in the top of the drug vial so thatpowdered or liquid drug may easily be inserted at this time into thedrug vial as by automated drug dispensing systems. Once an adequatevolume of powdered or liquid drug has been inserted into the drug vial,the distal stopper with its associated residual tether is inserted intothe top of the drug vial to occlude the opening in the drug vial. Thestopper may have a laterally projecting rim and a main stopper portionwhich can be received by a compression fit, as is known in the art, intothe glass opening to seal the opening. A distal sealing vial cover maythen be provided to sealingly retain the cap and drug within the vialfor long-term storage. After the vial cover has been removed, the distalstopper may be displaced from the glass opening by longitudinal forcedirected against the rim, away from the opening of the vial.

The distal vial stopper preferably includes flow channels. The flowchannels preferably do not provide communication of the vial chamberwith the atmosphere when the stopper is within the vial The flowchannels can be slots along the outer laterally projecting rim orperimeter of the stopper or can otherwise be through the stopper piston.The flow channels may be defined by the inner barrel wall and the distalstopper. The channels can be longitudinally slit valves or other valveswhich are tightly closed at rest, but which are opened by contact withthe distal end of the syringe. The laterally projecting portion of thedistal stopper preferably has a diameter exceeding the diameter of thesyringe bore so that the distal stopper is radially compressed by thebarrel and is tightly fit within the barrel by elastic compressionagainst the barrel wall. This allows for reliable fixation of the distalstopper within the barrel at the maximum point of advancement into thebarrel, which can be adjacent the distal end of the main barrel bore.This allows the vial to be reliably and easily opened within the barrelby single handle retraction. Since the distal stopper will be fixed bytight elastic compression and frictional engagement with the wall,longitudinal retraction force on the vial will displace the vial awayfrom the distal stopper.

In this way, each drug vial may be sized to be received intoconventional automated drug dispensing equipment and can be covered andmaintained for long-term storage within a conventional securely sealedpolymeric enclosure. The vial can then be connected with the handle andcan be packaged in a flexible sterile container along with the barrel,cannula, cannula cover, and even the diluent material in a singleflexible sterile packaging enclosure for shipment and storage. Thecomponents can be completely assembled within the closed or partiallyclosed sterile package immediately prior to use. This allows for easypackaging and storage and assures sterile assembly, which is otherwisedifficult to reliably achieve when loading a piston into a syringebarrel in an open environment.

As noted, in a preferred embodiment, the handle with its vial piston ispackaged with a separate syringe barrel within a single sterile flexibleenclosure and constructed so that the vial piston may be unsealed andloaded into the barrel within the same sterile package which was usedfor storage. To prepare the vial for activation, the pharmacist cangrasp a projecting tear tab on the sealing vial cover through theflexible package and remove the cover from the vial stopper, therebyexposing the enclosed distal stopper. The vial piston is then insertedinto the syringe barrel by contacting the outside of the barrel throughthe package and inserting the distal end of the vial piston into thebarrel. The vial piston is then fully advanced until the distal stoppercontacts the distal end. The cannula can then be inserted into aliquid-filled compartment or container within the sterile enclosure. Thevial piston can then be retracted. The syringe will then be filled byaspirating liquid enclosed within the enclosure into the barrel. Thefilled and mixed syringe can then be sent to the floor or to thepatient's home for use, or can be frozen for long-term storage, stillwithin the unopened and sealed original sterile enclosure.

In operation for injection, the handle is advanced until the distalstopper piston reaches a venting position along the barrel, if thehandle had not previously been advanced to that position duringassembly. The location of the venting position depends on the positionof the source of diluent. In the preferred embodiment, the ventingposition is adjacent the distal end of the barrel. However, if thediluent is positioned within the syringe, the venting position can be,for example, midway along the barrel. The handle is then retracted,pulling the drug vial away from the distal stopper which includes amember or portion which is tightly retained against a portion of thebarrel. This causes opening of the drug vial, thereby allowing fluid toflow into the drug vial and the drug to mix with fluid. In the preferredembodiment, the diluent fluid is stored external the syringe and theventing position is adjacent the distal end of the syringe barrel,leaving the distal stopper retained adjacent the distal end uponretraction of the vial. The distal stopper is preferably retained bytight frictional engagement with the smooth barrel or can be retained bydetents along the barrel. In embodiments utilizing a tensile element, asthe handle is further retracted, the tensile element will becomeextended, thereby transmitting tensile force to the proximal piston sothat further retraction of the handle and the attached vial will causethe proximal piston to be advanced relative to the retracting drug vialso that substantially all drug and solution within the vial is pusheddistally by the advancing proximal piston into the main bore or mixingchamber of the syringe. The vent preferably provides fluid communicationbetween the vial intermediate the proximal piston and the closed vialend, thereby relieving any negative pressure within the newly enlargingclosed proximal vial chamber by the passage of fluid or air through thevent into the vial proximal the proximal piston. After retraction, thesolution in the mixing chamber can be agitated. If preferred, an amountof air can be initially provided during manufacture within the vial tofacilitate agitation. Once the handle has been fully retracted, theproximal piston is received and retained within the distal end of thedrug vial, thereby occluding the distal end of the drug vial so that thedrug vial itself with its now distally occluding stopper piston now canfunction as a closed injection piston with the fully advanced proximalpiston as its distal face. The vial can be advanced to cause injectionof the mixed drug and solution into the patient with minimal residualremaining in the syringe. In one preferred embodiment, the diluentstored within the enlarging proximal chamber is later used to providesubsequent flushing of the syringe and can provide flushing of theinjected drug from the deadspace of the recipient tubing. Utilizing thisembodiment, during injection, once the vial piston has been fullyadvanced against the distal stopper, the proximal stopper is displacedfrom the end of the drug vial and the fluid which had been receivedthrough the vent and stored within the vial proximal the proximal pistonis now displaced by the forced movement of the proximal piston backtoward the closed end of the drug vial. Flow channels provided withinthe proximal piston allow displacement and flow of fluid from the drugvial chamber into the now virtually absent mixing chamber and out thedistal conduit to flush the syringe, the conduit, and the deadspace ofthe tubing which is connected to the conduit and which has previouslyreceived the drug solution mixture from the conduit. This embodiment,therefore, provides for: 1) enclosed sterile insertion of a handle andpiston assembly containing a powdered or liquid drug into a syringebarrel; 2) enclosed wide opening of the drug vial within the syringebarrel; 3) aspiration of diluent into free contact with the now exposeddrugs from within the vial and for positive expulsion of all drug fromwithin the vial; 4) aspiration of diluent which can later serve as aflush solution into an enlarging proximal chamber within the drug vial;5) injection of the mixed drug solution through or around the displacedstopper into the recipient; 6) injection of the flush solution throughthe distal portion of the syringe and out the distal conduit to flushthe syringe, the distal conduit, and at least a portion of the recipienttubing free of drug solution. It can be seen, therefore, that whether atensile element is utilized or whether the piston handle is connected tothe proximal piston, advancement of the proximal piston can be achievedfor positive expulsion of the drug and, at the same time, an enlargingproximal chamber is formed within the vial which can receive fluidswhich can subsequently be displaced back through the distal portion ofthe syringe to flush the syringe.

In one embodiment, the diluent is contained within the distal portion ofthe syringe for mixing within the drug vial. In another embodiment, thedistal conduit end of the syringe can be connected to a flexible bagcontaining a specific volume of diluent for aspiration into the syringewhich can be stored within or can be a compartment of the main enclosingflexible package for enclosed aspiration. The conduit can be placed influid connection with a fluid source through a cannula connected to thedistal end of the syringe. Alternatively, the fluid source may besealingly engaged to the syringe during manufacture and then enclosed ina main flexible package. Further, alternatively, a compartment of themain flexible package containing the diluent can be sealed about thedistal end of the syringe to minimize the amount of packaging requiredwhile further eliminating exposure during aspiration. A third embodimentutilizes a system wherein the syringe tip is inserted into a receiverhaving a one-way valve and connected to a multi-dose large volumereservoir of diluent in a hospital pharmacy of I.V. mixing area. Whendrug mixing is desired, the tip is inserted into the receiver and aspecific volume of diluent is aspirated. The maximum aspirated volumecan be preset by stops or by the length of the tether. The one-way valveprevents any potential for reflux of mixed drug solution into thereservoir.

In another preferred embodiment, the stopper assembly is providedincluding a connecting element intermediate the proximal piston and thedistal stopper. Like the previous embodiments, the embodiment preferablyincludes an inner wall defining a main bore and extending to a distaltip and a conduit extending through the distal tip. The distal stopperincludes projecting lateral walls for engaging. A seal is preferablyprovided occluding the conduit adjacent the distal tip. A diluentreservoir is further provided proximal the proximal piston and ispreferably contained within the handle of the syringe. The diluentreservoir is preferably a flexible bag of fluid and is comprised ofconventional material for making flexible intravenous bags of fluids,such as PVC. A flow passage way which can be a tubular extension of thePVC reservoir, is preferably provided through the proximal piston. Theflow passage way is occluded by the distal stopper or can preferably beoccluded by a cap which can be extracted from its occluding positionalong the flow passage way by the distal stopper. In the preferredembodiment, the distal stopper is integral with or is otherwise joinedwith the cap. The distal stopper preferably includes at least onemembrane such as projecting lateral walls engaging as by tightfrictional contact the inner wall or walls of the barrel, therebyeffectively fixing the position of the distal stopper piston at amaximally advanced position along the barrel which is preferablyadjacent the distal end of the barrel, although the position could bemidway along the barrel. The flexible fluid reservoir can contain thefirst pharmaceutical component, which is preferably diluent or liquiddrug. A second pharmaceutical component can be contained within theproximal portion of the barrel distal to the maximum advancing positionof the distal stopper or can be within a drug vial connectable to a drugvial connector carried by the proximal end of the reservoir. Theproximal end of the reservoir can include a reversibly sealed openingfor transferring fluid from the reservoir into the drug vial and fortransferring mixed drug and fluid out of the drug vial into thereservoir. In operation, the handle which has been advanced to a fullyadvanced position, is retracted. During retraction of the handle, thehandle with its retained reservoir and proximal piston are pulled awayfrom the distal stopper, thereby opening the distal end of the reservoirinto the barrel of the syringe. Continued retraction of the handleresults in negative pressure developing within the distal end of thesyringe, thereby withdrawing fluid from the open end of the reservoirinto the barrel. As the fluid is withdrawn, the flexible containercollapses until all of the fluid is withdrawn into the barrel, at whichtime further retraction cannot be accomplished due to the development ofa vacuum within the container. Furthermore, a detent can be providedwhich prevents further retraction to assure that excessive vacuum doesnot develop within the syringe. The flexible package dynamicallycollapses, thereby producing a collapsing valve mechanism preventingsubstantial transmission of negative pressure from the distal end of thesyringe to the drug vial; although, such transmission of negativepressure would not have significant adverse consequences with thepreferred embodiment in any regard. At this time, all of the mixed fluidand diluent have been displaced into a nascent mixing chamberintermediate the distal stopper and the proximal piston and subsequentlythis fluid can be injected by advancing the proximal piston, therebypushing the fluid through the flow channels and the distal stopper andout the distal end of the syringe after the seal has been removed fromthe distal end of the syringe. A one-way valve can be provided in theflow channel through the proximal piston to prevent reflux ordisplacement of fluids from the mixing chamber back into the flexiblereservoir during injection.

It is the purpose of the present invention to provide a drug injectorwhich can provide long-term storage of powdered or liquid drug andsubsequently allow enclosed mixing of this powdered or liquid drug witha diluent within the injector through a large opening to assure completeand easy mixing. It is the purpose of this invention to provide a distalvial stopper which can seal a reservoir or drug vial during storage, butwhich can provide a flow of fluid through or about the stopper once thereservoir or vial has been inserted into a syringe barrel and once thestopper has been displaced from the vial. It is further the purpose ofthis invention to provide a drug positioned between a piston stopperassembly connected by a tensile element within a vial so that the drugcan be pushed out of the vial into a mixing area by traction on thetensile element. It is further the purpose of this invention to providea closed drug vial which can be selectively widely opened within aclosed container to allow free mixing of the drug contained within thevial with a diluent. It is further the purpose of this invention toprovide a drug vial and piston stopper assembly wherein the drug vialfirst has a closed end containing the drug and wherein the end can beopened so that the drug can mix with a diluent and wherein the end canagain be subsequently closed so that the drug vial can function as adeadspace-free piston for injecting the mixed drug solution into thepatient. It is further the purpose of the invention to provide a syringehandle containing a drug vial and defining a drug vial piston within thesyringe. It is further the purpose of this invention to provide amulti-compartment injection system having a syringe barrel and a pistonand including a glass drug vial compartment for long-term storage of adrug, and a second compartment for storage of a specific volume ofdiluent and wherein the second compartment is sealed and can bepositioned inside or outside the syringe so that solution may bedisplaced into the vial to mix with the drug by retraction of the pistonalong the barrel and simultaneous unsealing of the vial or the diluentcompartment. It is further the purpose of this invention to provide adrug storage, mixing, and injection apparatus which allows long-termstorage of a drug within a glass vial comprehensively enclosed mixturewithin a syringe and then complete positive expulsion of all of thecontained drug into a mixing chamber within the syringe. It is furtherthe purpose of this invention to provide a system which allows positivedisplacement of diluent into a syringe compartment containing powdereddrug within an open-mouthed glass vial and subsequent injection of thediluent mixed with the drug utilizing closure and subsequent advancementof the glass vial within the syringe. It is further the purpose of thisinvention to provide a system and method for the enclosed sterileassembly of a drug mixing syringe and to provide a system for enclosedaspiration of fluid into the syringe for mixing with the drug within asingle inexpensive sterile flexible enclosure. It is further the purposeof the invention to provide a syringe which can sequentially aspirate adiluent and flush solution into two separate compartments, provide fordrug mixing with the diluent, and then provide sequential injection ofthe drug solution followed by the flush solution to flush substantiallyall drug from the syringe and to flush the injection site free of drugsolution. For some purposes, it is preferable to provide the diluent ina manner such that the diluent is packaged within a syringe componentwherein the drug vial can be packaged external to the syringe and wherefree and complete mixing between the drug vial and the diluent can beperformed within a syringe component. In one feature of the invention,the connection of a sealing capping member of the diluent reservoir to acap extraction member can fixedly engage a portion of the syringe barrelso that the cap can be extracted from the diluent reservoir byretraction of the diluent reservoir away from the fixed cap extractionmember connected to the cap. This allows enclosed opening of apreviously sealed diluent reservoir within the barrel of a syringe. Inanother feature of the invention, the cap extraction member includesflow channels for allowing passage of the mixed drug solution by the capextraction member and out the syringe. In another feature of theinvention, sealing occlusion of the distal tip of the syringe isprovided so that negative pressure induced within the syringe withdrawsfluid from a compartment proximal to the distal tip of the syringe,thereby withdrawing fluid into the syringe without the need for thefluid to be external and in fluid communication with the distal tip ofthe syringe. In another feature of the invention, the reservoir of fluidcan carry a drug vial engaging member for connecting the drug vial tothe diluent reservoir to allow free mixing between the drug vial and thediluent reservoir so that after the drug has been mixed with thediluent, the cap can be extracted by the cap extracting member and themixed drug solution can be withdrawn into the syringe by negativepressure induced within the syringe barrel. These and other featureswill become evident from the summary and detailed describe below.Furthermore, these and other objects and advantages of the inventionwill be further set forth in the description which follows and, in part,will be learned from the description or may be learned by practice ofthe invention. The objects and advantages of the invention may berealized by means of the instrumentalities and combinations particularlypointed out in the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an exploded view, in partial cross-section, of a syringeaccording to the present invention;

FIG. 1A is a top plan view of a distal stopper;

FIG. 1B is a bottom plan view of a distal stopper of FIG. 1A;

FIG. 1C is a cross-sectional view of the proximal and distal stopper andconnecting tether;

FIG. 2 is an exploded view, in partial cross section, of a syringeaccording to the present invention;

FIG. 2A is a perspective view of the detached vial piston end cover;

FIG. 3A is a partial cross-sectional view of the syringe as the plungeror vial piston is being inserted into the barrel;

FIG. 3B is a partial cross-sectional view similar to FIG. 3A, with theplunger fully inserted into the barrel;

FIG. 4A is a partial cross-sectional view similar to FIG. 3A, showingthe plunger being retracted;

FIG. 4B is a partial cross-sectional view similar to FIG. 3A, showingthe tether fully extended;

FIG. 4C is a partial cross-sectional view similar to FIG. 3A, showing arepositioned proximal stopper which is advanced relative to theretracted drug vial;

FIG. 5A is a partial cross-sectional view similar to FIG. 3A showing theplunger in an injection mode;

FIG. 5B is a partial cross-sectional view similar to FIG. 3A, showingthe completion of the injection;

FIG. 6 is an exploded view, in partial cross-section, of another syringeembodiment of the present invention;

FIG. 6A is a top plan view of a distal stopper;

FIG. 6B is a bottom plan view of a distal stopper;

FIG. 6C is an enlarged cross-sectional view of a proximal stopper;

FIG. 6D is an enlarged cross-sectional view of the distal stopper;

FIG. 7A is a cross-sectional view of a vial piston open and ready to befilled;

FIG. 7B is a partial cross-sectional view of the vial piston of FIG. 7A,mounted on a handle in a closed and sealed condition;

FIG. 7C is a top plan view of a sterile package for enclosed assemblyand aspiration;

FIG. 8A is a top plan view of another embodiment of a sterile packagingsystem, according to the present invention, showing a syringecompartment and a liquid compartment;

FIG. 8B is a top plan view similar to FIG. 8A, showing the syringe tipadvanced through a weakened sealed section in the package;

FIG. 8C is a cross-sectional view of the package, through lines 8C--8C,showing the upper and lower planar members;

FIG. 8D is a cross-sectional, view through lines 8D--8D, showing theweakened section between the fluid compartment and the syringecompartment, engaged by the distal tip of the syringe;

FIG. 8E is a cross-sectional view, similar to FIG. 8D, showing thesyringe tip pushed through the weakened section to enter the fluidcompartment;

FIG. 9 is an exploded view in partial section of another embodimentaccording to the present invention;

FIG. 9A is a top plan view of a distal stopper in the embodiment shownin FIG. 9;

FIG. 9B is a bottom plan view of the distal stopper, shown in FIG. 9A;

FIG. 9C is a cross-sectional view of a distal stopper, taken along lines9C--9C of FIG. 9B;

FIG. 9D is a top plan view of a proximal stopper in the embodiment ofFIG. 9;

FIG. 9E is a cross-sectional view taken along lines 9E--9E of FIG. 9D;

FIG. 9F is a cross-sectional view of the proximal and distal stopperused in FIG. 9 when interengaged during operation;

FIG. 10A is a partial cross-sectional view of the syringe of theembodiment of FIG. 9 with the plunger inserted into the barrel;

FIG. 10B is a partial cross-sectional view of the syringe of FIG. 9 withthe drug vial partially retracted;

FIG. 11A is a partial cross-sectional view of the syringe of FIG. 9 withthe drug vial fully retracted;

FIG. 11B is a partial cross-sectional view of the syringe of FIG. 9 withthe drug vial partially advanced as the mixed drug is injected;

FIG. 12A is a partial cross-sectional view of the syringe of FIG. 10 atthe initiation of the flush sequence;

FIG. 12B is a partial cross-sectional view of the syringe of FIG. 9 withthe plunger fully advanced at the conclusion of the drug injection andflushing;

FIG. 13 is an exploded cross-sectional view of a syringe, according toanother embodiment of the present invention having an integral drug vialand handle;

FIG. 14 is an exploded cross-sectional view of a syringe, according toanother embodiment of the present invention having a voluminous hollowhandle reservoir;

FIG. 14A is a top plan view of a distal stopper in the embodiment shownin FIG. 14;

FIG. 14B is a bottom plan view of the distal stopper, shown in FIG. 14A;

FIG. 14C is a cross-sectional view of the bottom and distal stoppersfrom the embodiment shown in FIG. 14;

FIG. 15 is a cross-sectional view of another embodiment of a syringe,according to the present invention;

FIG. 15A is an enlarged cross-sectional view of a portion of the distalend of the syringe of FIG. 15;

FIG. 15B is a cross-sectional view taken along line 15B--15B in FIG.15A;

FIG. 15C is a cross-sectional view taken along line 15C--15C in FIG. 15;

FIG. 15D is a cross-sectional view of another embodiment having a drugvial sized to be received within the syringe;

FIG. 15E is a cross-sectional view of the embodiment of FIG. 15D, afterthe stopper has been displaced into the flexible diluent container;

FIG. 15F is a cross-sectional view of the embodiment of FIG. 15D,showing withdrawal of the handle and displacement of liquid from theflexible container into contact with the syringe barrel;

FIG. 15G is a partial cross-section view according to the embodiment ofFIG. 15D, engaging a syringe pump and connecting to a catheter;

FIG. 16 is a partial cross-sectional view of another embodiment of asyringe, according to the present invention;

FIG. 16A is a top plan view of a distal stopper used in the embodimentshown in FIG. 16;

FIG. 16B is a cross-sectional view taken along line 16B--16B in FIG.16A;

FIG. 16C is a cross-sectional view of the proximal and distal pistonsfrom the embodiment of

FIG. 16 when interengaged during operation;

FIG. 17A is a top plan view of a sterile package showing a pleatedsyringe compartment;

FIG. 17B is a top plan view of the package of FIG. 17A with the syringehandle fully retracted;

FIG. 18A is a cross-sectional view of another embodiment of a syringe,according to the present invention;

FIG. 18B is a cross-sectional view of the embodiment of FIG. 18A withthe syringe handle partially retracted;

FIG. 18C is a cross-sectional view of FIG. 18B across lines C--C;

FIG. 18D is a cross-sectional view of the embodiment of FIG. 18A withthe handle fully retracted, demonstrating positive drug expulsion andconversion of the open-ended drug vial into a closed-ended piston;

FIG. 1BE is a cross-sectional view of the embodiment of FIG. 18A withthe handle partially advanced after complete retraction, demonstratingdrug solution injection by the now closed-ended drug vial.

DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS

For more easy understanding of the preferred embodiments, reference canbe made to the aforementioned co-pending patent application whichutilizes, for continuity and convenience, many similar figures andnumbers to the presently disclosed invention. With reference to onepreferred embodiment of the instant invention, a drug-mixing andinjection syringe 5 (shown disassembled in FIG. 1) has syringe barrel 10with inner wall 12 and smooth barrel bore 22. The barrel 10 extends todistal tapered end 14. The syringe 5 has a distal tip 18 and distalconduit 26 in fluid connection with bore 22. The syringe 5 furtherincludes handle 34 having a stop 35. A main vial piston 38 is providedincluding an outer housing 39 and having a distal sealing cover 45 andweakened tear regions 46, and projecting tear tab 48 enclosing a vial 50having a vial chamber 51 having an inner wall 52 and an outer wall 53.The vial 50 is preferably made of glass. The housing 39 and cover 45 canbe comprised of polypropylene or other suitable material. The main vialpiston 38 further includes an annular wiper or o-ring 54 for sealinglyengaging wall 12 of bore 22. The vial 50 includes a closed proximal end55 and a distal open end 60. The vial 50 contains a stopper pistonassembly 68, including proximal flexible, elastomeric piston 70 anddistal stopper or contact member 74. The vial piston 38 further includeshandle receiving recess 79 for receiving handle distal end 80, as shownin FIG. 1C. Piston 70 and stopper 74 are connected by a tether portion84 that includes a tether vent channel 86 extending between a proximalvent portion 87 and a distal vent portion 88. Stopper pistons 70 and 74are preferably comprised of conventional rubber stopper material. Thetether 84 is likewise comprised of conventional rubber so that it iscompatible with a variety of drugs and is flexible and capable oftransmitting tensile force. A silicone tubular rubber insert (not shown)may be used if desired within the tether 84 to provide added strengthand reduce stretching. Distal stopper 74 includes a distal face 75 and alateral projecting portion 76 and a proximal vial sealing portion 77.The wall portion 76 projects beyond the diameter of distal opening 60and the outer vial wall 52 of the drug vial 50 and includes multiplelateral flow channels 78 extending through the wall 76 and over the face75. These flow channels do not communicate with the vial chamber 51since a distal opening 60 of vial 50 is sealed by the side wall ofsealing portion 77. Therefore, flow channels 78 do not require a valveor other means for closure when the chamber 51 is sealed by the stopper74, thereby reducing both the cost of manufacture and the operatingcomplexity. The vial sealing portion 77 seals tightly about the distalvial end 60. The flow channels 78 are formed by the stopper 74 and thebarrel wall 12, but can otherwise be provided entirely through thestopper 74.

In assembly, the proximal piston 70 is fully advanced against the closedproximal end 55 of the vial 50. At this time, as shown in FIG. 7A, thetether 84 which preferably is longer than the vial 50 extends out theopen end 60 of the vial 50 and the distal stopper 74 is preferablypositioned away from the open end 60 of the vial 50 so that the vial 50can be filled with a powder or liquid drug. Once the drug vial 50 isfilled with powder or liquid drug, the vial sealing portion 77 of distalstopper 74 can be slightly compressed and inserted into the open distalend 60 of the drug vial 50 to provide a tight sealing fit. Vial 50further includes annular retainer 94, and proximal piston stop 96 fortightly retaining the proximal piston 70 in the fully advanced position,as will be described.

In operation, when mixture of the drug with a diluent is desired, thecover 45 (FIG. 2A) is removed by removing tear tab 48, the vial piston38 is then inserted into barrel 10 (FIG. 3A) and fully advanced againstthe end 14 of the barrel 10 (FIG. 3B). The distal stopper 74 is radiallycompressed by the barrel wall 12 to provide a tight friction fit and tofix the stopper 74 in the fully advanced venting position, as shown inFIG. 3B. The distal conduit 26 is then placed in fluid communicationwith a source of diluent, (such as that shown in FIG. 8B), if a sourceof diluent is not already attached adjacent the distal end 18 of thesyringe. The handle 34 is then retracted (FIG. 4A). As the handle 34 isretracted, the drug vial 50 is extracted away from the distal stopper 74since the distal stopper 74 is tightly held by tight compressivefrictional engagement of the laterally projecting portion 76 with thebarrel wall 12.

The retraction of the vial 50 forms a nascent mixing chamber 90intermediate the vial 50 and the distal stopper 74. The displacement ofthe distal stopper 74 out of sealing engagement with vial opening 60completely opens the vial chamber 51 into the enlarging nascent mixingchamber 90.

During this time, the negative pressure within the mixing chamber 90caused by retraction of the handle 34 causes diluent fluid to passthrough conduit 26, through the flow channels 78 of the distal stopper74 and on into the mixing chamber 90. As the mixing chamber 90 isenlarged, continued circumferential fluid flow enters the mixing chamber90 through the flow channels 78. As the handle 34 is further retracted,tether 84 becomes fully extended, as in FIG. 4B. After tether extension,further retraction of the handle 34 causes the vial 50 to be movedrelative to the now fixed proximal piston 70 so that the proximal piston70 advances and slides along inner wall 52 relative to the vial 50,thereby reducing vial chamber 51. This expels any liquid or solidcontents held within vial chamber 51 into the mixing chamber 90. Whenpiston handle 34 has been fully retracted (FIG. 4C), proximal piston 70engages stop 96 and is retained within the distal end 60 of the drugvial 50 by stop 96 and by retainer 94. In this position, as in FIG. 4C,proximal piston 70 now functions as a stopper and sealingly occludesdistal end 60 of drug vial 50, thereby converting the formerly widelyopen drug vial 50 into a closed injection piston 100 (FIG. 5A and FIG.5B). During relative advancement of the proximal piston 70 along vialwall 52, fluid can flow through the tether vent channel 86 from theconduit 26 into the enlarging reservoir 104 proximal to the piston 70within vial 50. This will fill the reservoir 104 with diluent. Thesyringe 5 can then be rocked or rolled to facilitate mixing. Gas can beinitially provided in the vial 50 with the drug during initialmanufacture and filling to enhance mixing after expulsion of the airfrom the vial chamber 51 along with the drug into the mixing chamber 90.All of the drug and solution is now contained within the mixing chamber90 and, therefore, should be visible through the barrel 22, which ispreferably comprised of relatively transparent polypropylene. This isadvantageous since residual clumps of powdered drug might otherwise becontained within the drug vial 50 and adequate mixing would not,therefore, be easily confirmable by visible inspection.

Some air, which was formerly present in the distal conduit and/or thedrug vial chamber 51 will also be present within the mixing chamber 90and will also allow for agitation of the mixing chamber 90 to assist inmixing of the drug and diluent.

To further facilitate adequate mixing, the syringe can be positioned sothat the distal tip 18 is in an upward position and the handle 34 can bemoved back and forth to facilitate mixing. Retraction of the handle 34is preferably limited by a proximal handle detent 110 along barrel 10which is positioned so that tether 84 is fully extended when proximaldetent 110 is engaged by the handle stop 35. This engagement preventsexcessive tensile force from being transmitted to the robber tether 84and assists in fixing the volume of diluent for mixing with the drug.

Once adequate mixing has been achieved and with the distal tip 18 in theupright position, any residual air can be expelled. The drug solutioncan then be injected (as depicted by the arrows (in FIG. 5A and FIG. 5B)or the syringe 5 can be capped for transport from the pharmacy to thenursing station for subsequent use.

In a preferred embodiment (shown in FIG. 7C), the syringe barrel 10 andthe piston handle 34 and vial piston 38 are enclosed within a singlesterile flexible plastic envelope 120 in an unassembled configurationwith an attached cannula 122 and a cannula cover 124. The plasticenvelope 120 is preferably of conventional flexible transparent andmedically sterilizable material, such as polyethylene orpolyvinylchloride, so that the syringe handle 34 and syringe barrel 10may be manipulated within the material for enclosed assembly within theenvelope 120. In operation, the projecting tear tab 48 is grasped by thethumb and forefinger through the flexible envelope 120 and the tear tab48 is held in position while the syringe handle 34 is rotated until thecover 45 is separated from the vial piston 38. The tear tab 48 can be1.5-2 centimeters or larger in length to provide ease in graspingthrough the envelope 120. The handle 34 and the barrel 10 are thengrasped and aligned within the envelope 120. The envelope 120 isprovided with sufficient length so as to allow room for such alignment.The handle 34 is then inserted into the barrel 10 and advanced until thedistal stopper 74 engages the distal end 14, as previously discussed.Assembly is then complete. The envelope 120 can then be opened, removed,and the conduit 26 placed in fluid communication with a source ofdiluent for aspiration of diluent into the syringe 5.

Alternatively, as in FIG. 7C, envelope 120 can include a compartment 130containing a sterile diluent, such as a saline or dextrose solution, anda syringe compartment 140 containing the syringe 5 components separatedfrom the fluid compartment 130 by a thermoformed seal or bond 145. Amembrane or septum 146 intermediate the compartments can be provided forpenetration by the distal tip 18 or an attached cannula 122 so thatdiluent could be directly aspirated from within the diluent compartment130 and so that the entire process could be accomplished within acompletely enclosed sterile environment. Alternatively, an inexpensivediluent container, as for example, a molded polypropylene bottle (notshown) can be enclosed with the syringe components in the main envelope120.

In a further embodiment (not shown), the syringe tip 18 may be sealinglycapped and packaged with the distal tip 18 projecting into, and sealedwithin, the diluent or fluid compartment 130. This allows simplifiedpackaging by placing the syringe tip 18 in a position such that thedividing seal 145 between the syringe compartment 140 and the diluentcompartment 130 extends across and includes the distal tip 18. With thisembodiment, the fluid compartment 130 may be only partially distended sothat the syringe cap or cover 124, which can include an additionalsealing cover (not shown), can be easily grasped through the fluid andenvelope 120 and removed to unseal conduit 26 at tip 18 when aspirationof fluid is desired. Once disengaged from tip 18, the cap or cover 124can be discarded within the compartment 130.

This comprehensively enclosed system is especially useful when thecontained drug is a chemotherapeutic agent, thereby greatly eliminatingoccupational exposure of even minute amounts of chemotherapeutic drugswherein cumulative occupational exposure may be hazardous to thehealthcare worker. It is further advantageous to utilize such assemblyof the syringe 5 within envelope 120 when the syringes are beingprepared and the drugs are being mixed within the syringes at a siteremote from the site of the syringes intended use or when there will bea significant delay between assembly and use. Examples include homehealthcare, mobile intensive care units, emergency medicine mobileunits, and in hospitals when preparation is performed in a centralizedpharmacy for distribution to floor units.

It can be seen that unless subsequent resterilization is contemplated,assembly of a syringe utilizing a sterile piston and handle and asterile barrel must be accomplished with care and generally must beaccomplished with sterile gloves and masks. This is so since contact ordroplet contamination of the handle could subsequently result in contactcontamination of the barrel, which later may be filled with solution,thereby resulting in contamination of the solution. In addition, duringstorage, organisms can potentially enter a stored assembled syringe fromthe barrel side and contaminate the syringe, especially if use of thesyringe is delayed. It would therefore be preferable, in situationsdescribed above, that the syringe be assembled and the drug mixed withsolution while the syringe is maintained within the original sterilecontainer. This effectively eliminates the need to repackage the syringefor later use, minimizes packaging cost and expense, and furthereliminates the need for assembly personnel to wear masks and gloveswhile handling the syringe and substantially reduces the risk ofpotential for exposure of the assembly personnel to drugs or otherpotentially toxic material which may be reconstituted within thesyringe. It should also be noted that liquid other than a diluent can beutilized and withdrawn into the syringe. For example, a drug solutionwhich can subsequently be mixed with the powdered or liquid drug withinthe vial can be provided and subsequently drawn into the syringe formixing, as described for the diluent.

In a further embodiment (as shown in FIG. 8A) for inexpensive enclosedpackaging and preparation, the syringe 5 is shown after assembly withina sealed, sterile transparent envelope 120' with the cover 45 removedfrom the vial piston 38 and the vial piston 38 inserted into the barrel10. Envelope 120' includes a syringe chamber 140' and a liquid chamber130'. The envelope 120' is preferably comprised of two planar sheets(FIG. 8C) of polyvinyl chloride, an upper sheet 122' and a lower sheet124'. These sheets are bonded or thermoformed to enclose the syringecompartment 140' and the liquid compartment 130'. A recess 144' isprovided intermediate the liquid compartment 130' and the syringecompartment 140'. A weakened sealed region 146' (shown in FIG. 8D) isprovided adjacent the liquid compartment 130' and the recess 144'. Inoperation, after the cover is removed from the vial piston 38 and thevial piston inserted into the barrel 10. Then, shown in FIG. 8D and FIG.8E, the syringe tip 18 may be inserted into the recess 144' andsubsequently wedge apart the weakened region 146' to enter the liquidcompartment 130'. At this time, the handle 34' can be retracted to drawfluid into the syringe 5. If preferred, another envelope 120" (such asis shown in FIG. 17A) can be provided with a pleated, bunched, foldedportion 150", or otherwise redundant portion to facilitate retraction ofthe handle 34. A tear or weakened portion 121" can be provided so thatthe envelope 120" can be removed once the fluid has been withdrawn intothe syringe 5 and the drug properly mixed with the fluid. It can be seenthat utilizing this comprehensive packaging system, the entire processcan be complete without exposing the syringe 5 to potentialcontamination to the environment and without exposing the preparingpersonnel to even minute quantities of drug.

Another preferred embodiment is shown in FIG. 6. This embodimentutilizes a cylindrical drug vial 50' which is open at the distal end 60'and the proximal end 55'. A distal piston 74' having circumferentialflow channels or slots 78', as described for the previous embodiment, issealingly received into the distal end 60' of vial 50'. A proximalpiston 70' includes a handle recess 79' for threadingly receiving athreaded end 80' of syringe handle 34'. The proximal piston 70' issealingly received into the proximal end 61'. A cover 45' havingweakened areas 46' and a tear tab 48' is provided over the proximalpiston 70' and extends over the distal stopper 74'. Upon removal of thetear tab 48' along the weakened areas 46', the entire cover 45' can beremoved from the vial piston 38'. Alternatively, separate proximal and adistal covers (not shown) could be provided with two separate tear tabs.A barrel 10' is provided with bore 22' having interior wall 12' forreceiving the vial piston 38'. A stop 35' can be provided on handle 34'to preset the volume of diluent to be aspirated into the barrel 10', aswill be described.

In assembly, a covered drug vial piston assembly 38', the handle 34',and the barrel 10' are preferably enclosed within a sterile envelope, aspreviously shown in FIG. 7C. If desired, at least one portion of theenvelope can include a region permeable to gas, such as Tyvek™, (notshown) for gas sterilization, as is known in the art. As notedpreviously, the sterile envelope is flexible and comprised, for example,of a material such as polyethylene or polyvinyl chloride, so that thecomponents Within the envelope can remain sterilely sealed yet be easilygrasped, manipulated, and assembled therein.

In operation, the tear tab 48' is grasped and the tear tab 48' and cover45' are removed from the vial piston assembly 38' The handle 34' is theninserted into recess 79' which can be threaded, as shown, to receive thehandle end 80' without substantial longitudinal force exerted againstthe proximal piston 70'. If preferred, the tear tab 48' is locatedadjacent proximal piston 70' of the vial piston assembly 38' so that theproximal portion of the cover 45' could first be removed, handle 34'threadably received into the recess 79', and handle 34' grasped for moreeasy removal of the distal portion of the cover 45' through a flexibleenvelope (such as is shown in FIG. 8A). Once the entire cover 45' isremoved, the piston assembly 38' and its attached handle 34' areinserted into the barrel 10' and fully advanced to the end of the barrel14'. As described in the previous embodiment, the projecting lateralwall 76' of distal stopper 74' is of greater diameter than the barrelbore 22' so that the lateral wall 76' can be pressed very tightlyagainst the interior wall 12' of the barrel 10'. This assures a tightfriction fit between the distal stopper 74' and the barrel 10' so that,while the piston 74' can be slidingly advanced by force along the barrel10' to the distal end 14'. Once positioned at the distal end of barrel10', piston 74' will stay in place. Consequently, upon retraction of thehandle, vial 50' will be extracted away from the distal stopper 74'since the position of distal stopper 74' is fixed by the fight fitagainst the barrel wall 12'. As the handle 34' is retracted, the distalend 60' is pulled away from stopper 74', thereby widely opening drugvial 50' and forming a mixing chamber intermediate the open-ended drugvial 50' and the distally retained distal stopper 74', as described andshown in the previous embodiments.

During this time, fluid can flow through the flow channels 78' adjacentthe distal stopper 74' to fill the mixing chamber and to mix drug withthe fluid entering through the flow channels 78'. When the handle 34'syringe has been fully retracted to draw the desired fluid volume intothe syringe, the syringe can be agitated to mix the drug with the fluid.The syringe conduit 26' can then be placed in fluid connection with theintended recipient of the drug and the piston handle 34' can beadvanced. As piston handle 34' is advanced, fluid exits the flowchannels 78' adjacent the distal stopper 74'.

The proximal piston 70' can be sized so that the frictional fit againstvial wall 52' induces less resistance to advancement than the frictionalfit of the wiper 54' against the inner barrel wall 12'. Therefore, uponadvancement of the handle 34', the proximal piston 70' first advancesalong vial wall 52' until it is fully advanced to seal the distal end60' of vial 50'. Retaining detents 94' can be provided to retain theproximal piston 70' in its fully advanced position at opening 60'against piston stop 96'. At this time, further advancement of handle 34'will cause the entire vial 50' with fully advanced piston 70' toadvance, thereby continuing the injection of fluid from the mixingchamber out the conduit 26' and into the intended recipient.

It is clear that many modifications may be made within the scope of thisteaching. For example, diluent could be stored within a portion of thesyringe, rather than external to the syringe. A bypass region anddetents could be provided along the syringe barrel to provide the flowchannel function, positioned at the distal end or midway along thesyringe. The syringe handle could be positioned within the barrel duringstorage. Hooks could be provided along the wall of the syringe forcatching the tear tabs upon rotation or advancement of the handle sothat the tear tab and sealing cover is automatically displaced from thedistal end of the syringe upon engagement of the hooks and rotation oradvancement of the handle, thereby separating the tight seal between thedrug vial and the cover within the syringe barrel. A tether valve can beprovided within the distal stopper, as described in the aforementionedpatent application Ser. No. 08/196,455 to allow a flow channel throughthe distal stopper when the distal stopper is fully advanced against theend of the syringe. The sealing fit of the distal stopper can beadjusted so that it is quite tight and the sealing fit of the proximalpiston within the drug vial can be adjusted so that it is quite loose,thereby assuring that the distal stopper will be retained in the distalend as the tether pulls the proximal stopper piston along the drug vialto expel the drug into the mixing chamber. It can be seen that, withsuch an embodiment if a tether and a valve are provided, the tether neednot be connected to the valve, but rather the valve may be designed toopen on contact with the distal end and remain open with the tetherbeing otherwise connected to the upper face of the distal stopper.

Another preferred embodiment, shown in FIG. 9, utilizes the previouslydescribed flow of liquid through the vent to allow storage of liquidwithin a proximal portion of the syringe for subsequent injection afterthe injection of the drug solution, thereby flushing the syringe and theinjection site free of drug solution. A syringe barrel 10" is providedwith bore 22" and inner wall 12". The handle 34" continues to include astop 35". The handle is connected to a vial piston assembly 38" having apolymeric portion 39" and a glass drug vial 50" with a closed proximalend 55" and an open distal end 60". The vial piston 38" includes cover45" having tear tab 48'. The vial piston 38" further includes a thincircumferentially extending rubber wiper sleeve 54". A proximalflexible, elastomeric stopper piston 70" is provided connected by atether 84" to a distal stopper or contact member 74". The distal stopper74" includes vial sealing portion 77" which seals tightly about innervial wall 52" at opening 60". The vial sealing portion 77" furtherincludes a series of longitudinal slots 150 which extend to a distal end156. A projecting wall portion 76" is provided having radiallyprojecting flow channel slots 78". These radial slots 78" are providedabout the entire perimeter of the lateral wall portion 76" so as toprovide complete circumferential fluid influx for more complete andrapid mixing of drug with the fluid to provide circumferential affix offluid to allow the drug solution to exit uniformly, and for the completecircumferential flush of drug solution from the syringe 10".

The proximal piston 70" includes several flow channels 160 and acontact-activated longitudinal slit or check valve 164 which includeslongitudinal slit or perforation 168. The entire proximal piston 70",including the slit valve 164, is preferably comprised of conventionalrubber stopper material. The slit valve 164 extends to a distal end ortip 170. The slit 168 is tightly closed or sealed at rest, preventingflow of fluid through from channel 160 out slit 168 and furtherpreventing flow in the reverse direction through slit 168 and into flowchannel 160.

Slit valve 164 will open upon forceful contact of tip 170 against distalstopper 74", as shown in FIG. 9F. This allows free fluid communicationbetween flow channels 160 and slots 150. Thus, the assembly defines adisplacement-activated medical check valve that selectively providesmedicinal fluid communication through proximal piston 74. The slitvalves preferably cannot be completely compressed so as to horizontallyclose slit 168 even with high pressure against distal piston 74". Thiscan be provided by including thickened walls 166 which provideresistance to excessive longitudinal compression, as proximal FIG. 9F.Further, this provides for a space 180 between proximal piston 70" anddistal piston 74", allowing free flow of fluid into longitudinal slots150, as will be described.

Tether 84", which again includes a tether vent, (as illustrated inprevious embodiments), is provided intermediate the proximal piston 70"and the distal piston 74", thereby connecting together the proximalpiston vent portion 87" and distal vent portion 88". The distal ventportion 88" can be compressed and closed by radial compression of thevial sealing portion 77", as by sloping inner vial wall 52" adjacent thedistal vial end 60" when the stopper 74" is sealingly engaged with thevial 50", as shown in FIG. 9.

In operation, the piston assembly 38" is loaded into the barrel 10" andadvanced, as shown in FIG. 10A. Distal conduit 26" is then connected toa source of diluent (if the source of diluent is not already attached tothe distal conduit end) and the handle 34" is retracted and the diluentis withdrawn into the syringe 5" since stopper 74" is retained by tightfrictional fit with the wall 12" and, thereby the drug vial 50" isextracted away from the stopper 74". As described for the previousembodiments, diluent flows through flow channels 78" defined by wallportions 76" and barrel wall 12" and into a nascent mixing chamber 90".With continued retraction, the tether 84" becomes extended (FIG. 11A),applying tensile force to the proximal piston 70" and effectivelyadvancing the proximal piston 70" along the drug vial 50".

As the proximal piston 70" advances along the drug vial 50", a nascentflush fluid chamber 104" is formed within drug vial 50", intermediatethe closed end 55" of drug vial 50" and the proximal piston 70". Whenaspiration is complete, mixing chamber 90" is filled with diluent anddrug and the flush chamber 104" is filled with flush solution. Thesyringe 5" is now ready for sequential injection and flush, as in FIG.11B. The distal conduit 26" is placed in fluid connection with areceiver, such as an intravenous saline well, as shown in theaforementioned patent application Ser. No. 08/196,455. The handle 34" isthen advanced (FIG. 12) and the drug solution is injected into therecipient. The drug solution flows from the mixing chamber 90" throughthe flow channel slots 78" and out the conduit 26". When slit valve 164contacts the distal piston 74" (as in FIG. 12A and FIG. 12B), the slits168 open, allowing fluid connection between space 180 and flushcompartment 104" through flow channels 160. As the handle 34" is furtheradvanced, the vial 50" passes over distal stopper 74", pushing proximalpiston 70" in a proximal direction, this compresses flush chamber 104"within vial 50" to force fluid out flow channels 160 through slits 168and into space 180, whereby the fluid flows through the distal stopperslots 150 and the adjacent drug vial wall 52" until the fluid escapespast distal end 60" of the drug vial and out radial slots 78" and distalstopper 74" and then through conduit 26". This effectively flushes theresidual drug from syringe 5" and further flushes the distal conduit 26"and its connecting receiver (such as a saline well, not shown) free ofdrug, thereby completing the drug injection and flush maneuver with asingle piston advancement.

It is clear that many modifications may be made to the aforementionedexemplary embodiments. For example, in another embodiment (shown in FIG.13), a drug vial 250 is integral with a handle 234 and detents 220 areprovided along barrel 210 for retaining the distal stopper 274 in adistal venting position adjacent bypass vents 278. In another embodiment(as shown in FIG. 14), the handle 234' can be hollow and contain a largesealed chamber 230' which can store and provide the sterile gas orliquid to relieve the negative pressure within the drug vial 250' whenthe proximal piston 270' is advanced along the drug vial 250'. Thiseliminates the need for a tether vent in tether 284. The large volumewithin the handle 234' allows the proximal piston 270' to advance withminimal negative pressure development within the drug vial 250' andhandle 234', thereby facilitating ease of advancement while maintaininga sealed environment. The handle 234' could alternatively store flushsolution and a one-way valve (not shown) could be provided intermediatethe vial 250' and the sealed handle chamber 230' so that fluidtransferred into the vial 250' from the handle 234' can later beselectively displaced into the barrel 210', as through slit valves inthe proximal piston (as shown in the previous embodiment) forsubsequently flushing of the syringe 205' after drug injection. Anotherembodiment (FIG. 16) shows contact-activated flush valves 464 on boththe proximal piston 470 and the distal stopper 274". This type of valvecan be used to replace the tether valve of my aforementioned patentapplication Ser. No. 08/196,455.

A further preferred embodiment is shown in FIG. 15. A drug-mixing andinjection syringe has a syringe barrel 10'" with inner wall 12'" and asmooth barrel bore 22'". The barrel 10'" extends to distal tapered end14'". The syringe 5'" has distal tip 18'" and distal conduit 26'" influid connection with bore 22'". The conduit 26'" is occluded by asealing cap or cover 19. The syringe further includes handle 34'" whichincludes a pair of opposing rigid support members 300 (which are alsoshown in FIG. 15C) extending to a distal retainer 310 for connection tothe proximal piston 70'". The support members 300 extend to a proximalend 320 which is bonded to drug vial receiving member 324 for receivingdrug vial 50'" having sealing plug 330. The handle 34'" further includesa flexible diluent reservoir 350 having a distal end 354 and a proximalend 358 and a folded or gathered region 359 adjacent the proximal end358. The proximal end 358 is occluded by reservoir plug member 360having a finger contact rim 364 and a including a male vial plugengaging member 368 for retentive engagement with vial plug 330. Thesupport members 300 are spaced apart to define intermediate fingercontact windows 366 for allowing direct finger contact of flexiblereservoir 350 adjacent contact rim 364 to allow easy displacement ofplug 360, as will be discussed.

The flexible fluid reservoir 350 includes a inner chamber 370. The innerchamber 370 is in fluid connection with tube 374 (FIG. 15A), defining alumen 378 extending to a distal lumen opening 380. A one-way valve 384,shown generically in FIG. 15A, is provided within the lumen 378 foroccluding the lumen 378. The one-way valve 384 can be one of any numberof conventional one-way valves which are opened by relative negativepressure distal the one-way valve 384 and which are closed by relativepositive pressure distal the one-way valve 384. For example, a ball andcage valve, a flap valve (as utilizing a thin, flexible polymeric orrobber flap, the deflection of which is responsive to a pressuredifferential across the flap), or other conventional valve may beutilized. The lumen 378 of tube 374 is occluded by sealing cap 390connected to distal stopper 74'". As described for the previouslydiscussed embodiments, a piston stopper assembly 68'" is provided andshown enlarged in FIG. 15A. The piston stopper assembly 68'" includesdistal stopper 74'" and proximal piston 70'". Prior to use, distalstopper 74'" and proximal piston 70'" are connected by tube 374, whichthereby comprises a connecting element. As with the previousembodiments, distal stopper 74'" includes radial flow channels or slots78'". The distal stopper 74'" has a diameter which is greater than thediameter of bore 22'" so that distal stopper 74'" is compressablyreceived within bore 22'" to provide a tight frictional fit againstinner Wall 12'". Distal stopper 74'" is, therefore, fixedly engaged withinner wall 12'" after distal stopper 74'" has been forcibly advanced tothe maximum position within the barrel 10'" adjacent barrel end 14'".

As shown in FIG. 15D, a flange 395 may be provided adjacent the drugvial 350 to allow the drug vial 350 and handle 34'" to be more easilyretracted and advanced. The flange 395 can be sized to be receivedwithin an automatic, mechanical, or electronic syringe pump 398 (FIG.15G). Furthermore, as shown in FIG. 15D, the drug vial 350 can be sizedto be slidably received within the syringe barrel 10'" for moreconventional operation and ease of interface with conventional syringepumps. If preferred, for interfacing with syringe pumps, a neck (notshown) having the configuration of a conventional syringe handle can beprovided intermediate the flange 395 and adjacent the drug vial 350 tofacilitate operation with conventional syringe pump designs.

In operation, drug vial 50'" with the attached sealing plug 330 isthreadably engaged with the drug vial retainer 324 so that plug 330 istightly retained about reservoir plug 360 (FIG. 15E) prior to completeinsertion into barrel 10'" of handle 34'". The user can then contactplug rim 364 through windows 366 and advance plug 360 distally so thatthe reservoir plug 360 and the retained vial plug 330 are displaced awayfrom vial opening 60'". Diluent from reservoir 370 can then freely flowinto drug vial chamber 51'" through opening 60'" to mix the drugformerly retained within the vial 50'" and the diluent formerly retainedwithin the reservoir 350. Free flow of diluent and mixed solution can beachieved through the large vial opening 60'". The syringe 5'" can berocked and rolled so as to provide complete mixing. Once mixing iscomplete, handle 34'" can be grasped and retracted. Retraction of handle34'" will cause proximal piston 70'" to be displaced away from theretained distal stopper 74'" so that cap 390 is disengaged from tube374.

In addition, negative pressure within bore 22'" will develop sinceconduit 26'" is sealed by cap 19. This will open one-way valve 384 tocause the mixed drug solution contained within the reservoir 350 andvial 50'" to flow into the syringe barrel bore 22'" through the nowopened lumen 378. Once all of the fluid has been displaced into thebarrel 22'", further retraction of handle 34'" is inhibited by thedevelopment of negative pressure within the barrel 22'" distal to piston70'". The retraction maneuver is preferably performed with the syringe5'" in a position wherein the distal tip 18'" is directed downward toassist in the free flow of fluid out lumen 378 and into contact withinner barrel wall 12'". Upon complete withdrawal of handle 34'" (FIG.15F), flexible reservoir 350 has collapsed, effectively reducing thetransmission of negative pressure from within the syringe barrel 22" towithin the drug vial 50'", although such transmission of negativepressure is not seen as detrimental with the presently preferredembodiment. After the mixed drug solution has been drawn within bore22'" into contact with the barrel wall 12'" distal the retractedproximal piston 70'", the drug solution is ready for injection. Distaltip cap 19 can then be removed and conduit 26'" placed in fluidconnection with the intended recipient of the drug solution forsubsequent injection of the drug solution. The drug solution is injectedby advancing handle 34'", thereby advancing proximal piston 70'". Duringadvancement, positive pressure within bore 22'" distal the proximalpiston 70'" causes the one-way 384 to close so that drug solution doesnot reflux through lumen 378 back into reservoir 350. A potential toreduce development costs by interfacing with a variety of conventionaldrug vial systems provides a substantial value to this presentembodiment.

A further embodiment (shown in FIG. 18A), functions in a manner similarto the embodiment of FIG. 6, but having the advantage of providing forpositive displacement of a proximal piston along an inner drug vial wallto displace the drug from the drug vial, as will be discussed. Thisembodiment, (numbered similar to FIG. 6, but with 600s) utilizes a vialpiston assembly 638 including a cylindrical drug vial 650 which is openat a distal end 660 and a proximal end 661. A distal piston 674 havingcircumferential flow channels or slots 678 is sealingly received intothe distal end 660 of vial 650. The proximal piston 670 is sealinglyreceived into the proximal end 661. A barrel 610 is provided with a bore622, having an inner wall 612 for receiving a slideable rubber,circumferential, sealing wiper 654 surrounding the drug vial 650. Ahandle 634 is provided, having distal retainers 636 for retaining thehandle 634 within the circumferential wiper 654. A stop-rod 680 isprovided, having a pair of proximal stops 682 and a threaded distal end684. The threaded end 684 is sized to be threadably received withinproximal stopper 670. The stop-rod slides within opposing slots 685 and686 along handle 634. The length of slots 685 and 686 is equal to therelative displacement length of the proximal piston 670 along drug vial650, as will be described. The stops 682 are sized to engage a proximaldetent 688 along barrel 610 upon retraction of handle 634. The operationof this embodiment is quite similar to the embodiment of FIG. 6, exceptthat this syringe 605 provides positive displacement of the contents ofdrug vial 650 into the mixing chamber 690 upon retraction of handle 634,as will be discussed.

In initial assembly, the handle 634 and attached vial piston assembly638 is loaded into the syringe barrel 610 and fully advanced to thedistal tapered end 614. As previously discussed for earlier embodiments,the distal stopper 674 has a greater diameter than the syringe barrelbore 622 so that the distal stopper 674 is compressed by the syringebarrel 610 to provide tight frictional engagement in the maximallyadvanced position of FIG. 18A. Withdrawal of handle 634, as in FIG. 18B,causes drug vial 650 to be displaced away from distal stopper 674 towidely open the drug vial chamber 651 into a nascent mixing chamber 690.In addition, retraction of handle 634 causes negative pressure todevelop in chamber 690 and thereby causes fluid to flow through conduit626 and through slots 678 into mixing chamber 690. During the retractionof handle 634 and the attached drug vial 650, the stop-rod 680 isslidably displaced along slots 685 and 686. As shown in FIG. 18D,further retraction of handle 634 and the attached vial 650 causes stops682 to engage annular detent 688, thereby causing positive relativeadvancement of stop-rod 680 and the attached piston 670 along drug vialwall 652 and past drug vial detent 694 so that the proximal piston 670is retained adjacent the distal end 660 of drug vial 650. Once handle634 has been fully retracted and stop-rod 680 and attached proximalpiston 670 has been fully advanced along drug vial wall 652,substantially all of the drug formerly contained within drug vialchamber 651 has been positively expressed into nascent mixing chamber690. The syringe 605 can then be agitated to facilitate mixing.

When injection is desired, the distal conduit 626 through distal tip 618can be placed in fluid connection with the intended recipient. Thehandle 634 is then advanced. The proximal piston 670 and the stop-rod680 are prevented from proximal displacement by retainer 694.Alternatively, complementing detents (now shown) could be provided alongthe slots 685 and 686 and stop-rod 680 to prevent displacement of theproximal piston 670 once the proximal piston 670 has been advanced alongthe vial 650, thereby eliminating the need for the vial retainers 694.During advancement, the drug solution contained within mixing chamber690 is pushed through slots 678, out conduit 626, and into the intendedrecipient. It can be seen that the operation of this embodiment allowspositive displacement of substantially all drug out of a drug vial 650and into a mixing chamber 690 within a syringe 605 with a single handle634 retraction maneuver. The embodiment further does not require the useof a tether, as described for some of the previous embodiments. Thisembodiment, therefore, has the advantage of simplified operation andmanufacture. Markers or detents (not shown) can be provided along thehandle 634 and the syringe barrel 610 for indicating that completewithdrawal and locking of the proximal piston 670 in the fully advancedposition of FIG. 18D has been achieved.

Although the presently preferred embodiments of this invention have beendescribed, it will be obvious to those skilled in the art that variouschanges and modifications may be made therein without departing from theinvention. Therefore, the claims are intended to include all suchchanges and modifications which may be made therein without departingfrom the invention. Therefore, the claims are intended to include allsuch changes and modifications that fall within the true spirit andscope of the invention.

I claim:
 1. A displacement-activated medical check valve for selectivelyopening and closing medicinal fluid communication, the check valvecomprising:a. a flexible elastomeric member having a proximal end and adistal end and further having a sealed perforation at least partiallythrough said member; b. a housing defining a bore for receiving saidmember, said bore having a longitudinal axis, said member being sizedsuch that at least a portion of said elastomeric member is displaceablealong the longitudinal axis of said bore; c. a contact member sized andconfigured for engaging said distal end of said elastomeric member whenat least a portion of said elastomeric member is displaced against saidcontact member; d. said elastomeric member and said sealed perforationbeing sized and configured such that said perforation is shortened andthereby compressed open when said elastomeric member is compressedagainst said contact member, said elastomeric member rebounding to closesaid perforation when said elastomeric member is free from compressiveforce so that fluid may flow through said perforation when saidelastomeric member is compressed but fluid is prevented from flowingthrough said perforation when said elastomeric member is free fromcompressive force.
 2. The check valve of claim 1, wherein saidperforation is a slit.
 3. The check valve of claim 2, wherein saidelastomeric member is elongated to define a longitudinal axis, said slitextending along said axis.
 4. The check valve of claim 3, wherein saidslit extends through said elastomeric member adjacent said distal end.5. The check valve of claim 4, wherein said distal end is configured todefine a narrow distal tip for compression against said contact member.6. The check valve of claim 2, wherein said slit extends through saidelastomeric member adjacent said distal end.
 7. The check valve of claim1, wherein said perforation extends through said member adjacent saiddistal end.
 8. The check valve of claim 7, wherein said distal end isconfigured to define a narrow distal tip for compression against saidcontact member.
 9. The check valve of claim 1, wherein said contactmember is rigid.
 10. The check valve of claim 1, wherein said entireelastomeric member is slidable along said bore to engage said contactmember.
 11. The check valve of claim 1, wherein said contact member ismounted adjacent said bore.
 12. The check valve of claim 1, wherein saidcontact member is mounted adjacent said bore.
 13. Thedisplacement-activated medical check valve as in claim 1 wherein saidcompression is in a longitudinal direction.
 14. Thedisplacement-activated medical check valve as in claim 1, wherein thecontact member includes a distal conduit whereby fluid can flow throughsaid valve and out said conduit.
 15. The displacement-activated medicalcheck valve as in claim 14, wherein said distal conduit is in fluidcommunication with said bore.
 16. The displacement-activated medicalcheck valve as in claim 14, wherein said distal conduit is defined so asto extend centrally along said longitudinal axis of said bore.w